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Lung cancer AND CDK

Yi-Fan Chen, Jonathan J Cho, Tsai-Hua Huang, Chao-Neng Tseng, Eng-Yen Huang, Chung-Lung Cho
ROGDI is a protein that contains a leucine zipper domain and may be involved in cell proliferation. In addition, ROGDI is associated with genome stability by regulating the activity of a DNA damage marker, γ-H2AX. The role of ROGDI in tumor radiosensitization has not been investigated. Previous studies have indicated that radiosensitivity is associated with DNA repair and the cell cycle. In general, the G2/M DNA damage checkpoint is more sensitive to radiation, whereas the G1/S phase transition is more resistant to radiation...
August 12, 2016: Cancer Biology & Therapy
Robert J D Reid, Xing Du, Ivana Sunjevaric, Vinayak Rayannavar, John Dittmar, Eric Bryant, Matthew Maurer, Rodney Rothstein
The CKS1B gene located on chromosome 1q21 is frequently amplified in breast, lung, and liver cancers. CKS1B codes for a conserved regulatory subunit of cyclin-CDK complexes that function at multiple stages of cell cycle progression. We used a high throughput screening protocol to mimic cancer-related overexpression in a library of Saccharomyces cerevisiae mutants to identify genes whose functions become essential only when CKS1 is overexpressed, a synthetic dosage lethal (SDL) interaction. Mutations in multiple genes affecting mitotic entry and mitotic exit are highly enriched in the set of SDL interactions...
October 2016: Genetics
Alexey V Danilov, Shanhu Hu, Bernardo Orr, Kristina Godek, Lisa Maria Mustachio, David Sekula, Xi Liu, Masanori Kawakami, Faye M Johnson, Duane A Compton, Sarah J Freemantle, Ethan Dmitrovsky
Despite advances in targeted therapy, lung cancer remains the most common cause of cancer-related mortality in the United States. Chromosomal instability is a prominent feature in lung cancer and because it rarely occurs in normal cells, it represents a potential therapeutic target. Our prior work discovered that lung cancer cells undergo anaphase catastrophe in response to inhibition of cyclin-dependent kinase 2 (CDK2), followed by apoptosis and reduced tumor cell growth. In this study, the effects and mechanisms of the multi-CDK inhibitor dinaciclib on lung cancer cells were investigated...
August 22, 2016: Molecular Cancer Therapeutics
Pei-Shi Ong, Lingzhi Wang, Deborah Miao-Hui Chia, Jolyn Yu-Xin Seah, Li-Ren Kong, Win-Lwin Thuya, Arunachalam Chinnathambi, Jie-Ying Amelia Lau, Andrea Li-Ann Wong, Wei-Peng Yong, Daiwen Yang, Paul Chi-Lui Ho, Gautam Sethi, Boon-Cher Goh
With conventional anticancer agents for non-small cell lung cancer (NSCLC) reaching therapeutic ceiling, the novel combination using histone deacetylase inhibitor, PXD101 (Belinostat(®)), and CDK inhibitor, CYC202 (Seliciclib(®)), was investigated as an alternative anticancer strategy. At clinically achievable concentration of CYC202 (15 µM), combination therapy resulted in significant reduction in cell proliferation (IC50 = 3.67 ± 0.80 µM, p < 0.05) compared with PXD101 alone (IC50 = 6...
October 10, 2016: Cancer Letters
Amita Patnaik, Lee S Rosen, Sara M Tolaney, Anthony W Tolcher, Jonathan W Goldman, Leena Gandhi, Kyriakos P Papadopoulos, Muralidhar Beeram, Drew W Rasco, John F Hilton, Aejaz Nasir, Richard P Beckmann, Andrew E Schade, Angie D Fulford, Tuan S Nguyen, Ricardo Martinez, Palaniappan Kulanthaivel, Lily Q Li, Martin Frenzel, Damien M Cronier, Edward M Chan, Keith T Flaherty, Patrick Y Wen, Geoffrey I Shapiro
UNLABELLED: We evaluated the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of abemaciclib, an orally bioavailable inhibitor of cyclin-dependent kinases (CDK) 4 and 6, in a multicenter study including phase I dose escalation followed by tumor-specific cohorts for breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, melanoma, and colorectal cancer. A total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts...
July 2016: Cancer Discovery
Yin-Wen Shiue, Chi-Cheng Lu, Yu-Ping Hsiao, Ching-Lung Liao, Jing-Pin Lin, Kuang-Chi Lai, Chien-Chih Yu, Yi-Ping Huang, Heng-Chien Ho, Jing-Gung Chung
Casticin, a polymethoxyflavone occurring in natural plants, has been shown to have anticancer activities. In the present study, we aims to investigate the anti-skin cancer activity of casticin on melanoma cells in vitro and the antitumor effect of casticin on human melanoma xenografts in nu/nu mice in vivo. A flow cytometric assay was performed to detect expression of viable cells, cell cycles, reactive oxygen species production, levels of [Formula: see text] and caspase activity. A Western blotting assay and confocal laser microscope examination were performed to detect expression of protein levels...
2016: American Journal of Chinese Medicine
Ying Xing, Qingwei Meng, Xuesong Chen, Yanbin Zhao, Wei Liu, Jing Hu, Feng Xue, Xiaoyuan Wang, Li Cai
Tripartite motif-containing protein 44 (TRIM44) was recently identified as a potential therapeutic target in several types of malignancy, but its effect on the clinical course of malignancy and its underlying regulatory mechanism remain largely unknown. The present study shows that upregulation of TRIM44 is associated with poor differentiation, advanced pTNM stage, adenocarcinoma subtype, lymph node metastasis and, most importantly, unfavorable survival in patients with non-small cell lung cancer (NSCLC). TRIM44 knockdown inhibited the invasion and migration of human NSCLC cells, which was concurrent with downregulation of mesenchymal markers and upregulation of epithelial markers...
May 24, 2016: Oncotarget
Weizhen Zhang, Zhenyu Liang, Jing Li
Lung cancer is the leading cause for cancer-related death, however, the pathogenesis mechanism is poorly understood. Although the rhotekin (RTKN) gene has been reported to encode an effector for the Rho protein that has critical roles in regulating cell growth, the role of RTKN in lung cancer has not been investigated. In clinical lung cancer patient tumor samples, we identified that the RTKN gene expression level was significantly higher in tumor tissues compared to that of the adjacent normal tissues. To investigate the molecular mechanisms of RTKN in lung cancer, we established RTKN stable knock-down A549 and SPC-A-1 lung adenocarcinoma cell lines using lentiviral transfection of RTKN shRNA and evaluated the antitumor effects...
May 2016: Oncology Reports
Kanglai Wei, Zhihua Ye, Zuyun Li, Yiwu Dang, Xin Chen, Na Huang, Chongxi Bao, Tingqing Gan, Lihua Yang, Gang Chen
BACKGROUND: Cyclin-dependent kinase 5 (CDK5) is an atypical CDK which plays a vital role in several cancers via regulating migration and motility of cancer cells. However, the clinicopathological impact and function of CDK5 in lung cancer remain poorly understood. The present study was aimed at exploring expression and clinicopathological significance of CDK5 in lung cancer. METHODS: There were 395 samples of lung tissue including 365 lung tumors (339 non-small cell lung cancers and 26 small cell lung cancers) and 30 samples of normal lung...
2016: World Journal of Surgical Oncology
P Lalitha, V Veena, P Vidhyapriya, Pragna Lakshmi, R Krishna, N Sakthivel
Marine bacterium, strain MB30 isolated from the deep sea sediment of Bay of Bengal, India, exhibited antimicrobial activity against human pathogenic bacteria. Based on the 16S rRNA sequence homology and subsequent phylogenetic tree analysis, the strain MB30 was identified as Staphylococcus sp. The bioactive metabolite produced by the strain MB30 was purified through silica gel column chromatography and preparative HPLC. Purified metabolite was further characterized by FT-IR, LC-MS and NMR analyses. On the basis of spectroscopic data, the metabolite was identified as pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2-methyl propyl) (PPDHMP)...
May 2016: Apoptosis: An International Journal on Programmed Cell Death
Joon Seok Byun, Joo Mi Sohn, Dong Gyu Leem, Byeongyeon Park, Ji Hye Nam, Dong Hyun Shin, Ji Sun Shin, Hyoung Ja Kim, Kyung-Tae Lee, Jae Yeol Lee
As a result of our continuous research, new 3,4-dihydroquinazoline derivative containing ureido group, KCP10043F was synthesized and evaluated for T-type Ca(2+) channel (Cav3.1) blockade, cytotoxicity, and cell cycle arrest against human non-small cell lung (A549) cells. KCP10043F showed both weaker T-type Ca(2+) channel blocking activity and less cytotoxicity against A549 cells than parent compound KYS05090S [4-(benzylcarbamoylmethyl)-3-(4-biphenylyl)-2-(N,N',N'-trimethyl-1,5-pentanediamino)-3,4-dihydroquinazoline 2 hydrochloride], but it exhibited more potent G1-phase arrest than KYS05090S in A549 cells...
February 1, 2016: Bioorganic & Medicinal Chemistry Letters
Hun Seok Lee, Juthika Kundu, Ryong Nam Kim, Young Kee Shin
Transducer of ERBB2.1 (TOB1) is a tumor-suppressor protein, which functions as a negative regulator of the receptor tyrosine-kinase ERBB2. As most of the other tumor suppressor proteins, TOB1 is inactivated in many human cancers. Homozygous deletion of TOB1 in mice is reported to be responsible for cancer development in the lung, liver, and lymph node, whereas the ectopic overexpression of TOB1 shows anti-proliferation, and a decrease in the migration and invasion abilities on cancer cells. Biochemical studies revealed that the anti-proliferative activity of TOB1 involves mRNA deadenylation and is associated with the reduction of both cyclin D1 and cyclin-dependent kinase (CDK) expressions and the induction of CDK inhibitors...
2015: International Journal of Molecular Sciences
Nicola J Grant, Philip J Coates, Yvonne L Woods, Susan E Bray, Nicholas A Morrice, C James Hastie, Douglas J Lamont, Francis A Carey, Calum Sutherland
BACKGROUND: Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult...
2015: BMC Cancer
Lin Su, Dongrui Han, Jingwen Wu, Xueyun Huo
Maternally expressed gene 3 (Meg3) encodes a long non-coding RNA that has been shown to play a role in tumorigenesis. Skp2 is a component of the E3 ubiquitin ligase SCF that specifically promotes the ubiquitination-associated degradation of CDK inhibitor p27, and has been shown to promote cancer cell growth in different types of cancers, including non-small cell lung cancer (NSCLC). Nevertheless, a regulatory relationship between Meg3 and Skp2 has not been acknowledged. Here, we showed that NSCLC specimens had significant higher levels of Skp2 and significantly lower levels of Meg3, compared to paired non-tumor lung tissue...
March 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Shanhu Hu, Yun Lu, Bernardo Orr, Kristina Godek, Lisa Maria Mustachio, Masanori Kawakami, David Sekula, Duane A Compton, Sarah Freemantle, Ethan Dmitrovsky
Chromosomal instability (CIN) is a hallmark of solid tumor biology and is implicated in carcinogenesis. Preferentially eliminating malignant cells by targeting CIN and aneuploidy is an attractive antineoplastic strategy. We previously reported that CDK2 antagonism causes lung cancer cells to undergo anaphase catastrophe and apoptosis through inhibition of phosphorylation of the centrosomal protein CP110. Cells with activating KRAS mutations were particularly sensitive to CDK2 inhibition due to downregulation of CP110 protein levels...
November 2015: Molecular Cancer Therapeutics
Xue-Jiao Lv, Li-Jing Zhao, Yu-Qiu Hao, Zhen-Zhong Su, Jun-Yao Li, Yan-Wei Du, Jie Zhang
Lung cancer is the leading cause of cancer death in the world. Schizandrin B (Sch B) is one of the main dibenzocyclooctadiene lignans present in the fruit of Schisandra chinensis (Schisandraceae). Sch B has multiple functions against cancer. The aim of this study was to determine the effect of Sch B on the proliferation, cell cycling, apoptosis and invasion of lung adenocarcinoma A549 cells by MTT, flow cytometry, wound healing and transwell invasion assays. Treatment with Sch B inhibited the proliferation of A549 cells in a dose-dependent manner...
2015: International Journal of Clinical and Experimental Medicine
M Kolodziej, C Goetz, P Di Fazio, R Montalbano, M Ocker, H Strik, K Quint
Purine analogue roscovitine, a cyclin-dependent kinase (CDK) inhibitor, has shown strong anti-proliferative and pro-apoptotic effects in solid and hematologic cancers such as non small-cell lung cancer and lymphomas. It targets CDK2, 7 and 9 preferentially, which are also overexpressed in glioblastoma. Τherefore, the biological effects of roscovitine in glioblastoma cell lines were investigated. Glioblastoma A172 and G28 cell lines were incubated with serial concentrations of roscovitine for 24-120 h. Proliferation was measured using the xCELLigence Real-Time Cell Analyzer, an impedance‑based cell viability system...
September 2015: Oncology Reports
Sourav Sikdar, Avinaba Mukherjee, Anisur Rahman Khuda-Bukhsh
BACKGROUND: Marsdenia condurango (condurango) is a tropical woody vine native to South America. Our earlier study was limited to evaluation of anti-cancer potentials of crude condurango extract and its glycoside-rich components in vitro on lung cancer. OBJECTIVE: This study aims at evaluating the effect of the single isolated active ingredient condurangogenin A (ConA; C32H42O7) on A549, H522 and H460-nonsmall-cell lung cancer cells. MATERIALS AND METHODS: ConA was isolated by column chromatography and analyzed by mass spectroscopy, Fourier transform infrared spectroscopy and proton-nuclear magnetic resonance...
May 2015: Pharmacognosy Magazine
Ji Hyung Hong, Kang San Roh, Sung-Suk Suh, Sukchan Lee, Sook Whan Sung, Jae Kil Park, Jae Ho Byun, Jin Hyoung Kang
We aimed to establish whether the expression of microRNA-34a (miR-34a) is correlated with that of c-MET and G1 phase regulators such as cyclin dependent kinase (CDK) 4, CDK6, and cyclin D (CCND) 1 in non-small cell lung cancer (NSCLC), and whether a relationship exists between miR-34a expression and both clinicopathologic factors and recurrence-free survival (RFS). For 58 samples archived from NSCLC patients, we measured the expression of miR-34a and c-MET, CDK4/6, and CCND1 by quantitative RT-PCR and assessed the relationship between miR-34a expression, clinicopathological factors, and RFS...
December 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Carmela De Marco, Donatella Malanga, Nicola Rinaldo, Fernanda De Vita, Marianna Scrima, Sara Lovisa, Linda Fabris, Maria Vincenza Carriero, Renato Franco, Antonia Rizzuto, Gustavo Baldassarre, Giuseppe Viglietto
The hotspot E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. In this manuscript, we sought to determine whether this AKT1 variant is a bona-fide activating mutation and plays a role in the development of lung cancer. Here we report that in immortalized human bronchial epithelial cells (BEAS-2B cells) mutant AKT1-E17K promotes anchorage-dependent and -independent proliferation, increases the ability to migrate, invade as well as to survive and duplicate in stressful conditions, leading to the emergency of cells endowed with the capability to form aggressive tumours at high efficiency...
November 24, 2015: Oncotarget
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